This program represents a multi-institutional collaborative multidisciplinary approach to improving the treatment of both acute lymphocytic leukemia and acute myelogenous leukemia. The chemotherapy innovations will involve intensive and rotational therapy of chemotherapeutic agents in remission in patients with AML in an attempt to maximize leukemia cytoreduction and minimize the development of drug resistance. In acute lymphocytic leukemia the major chemotherapeutic thrust will relate to the development of modified and new programs for prognostic subcategories of ALL. It will in addition include new approaches to control meningeal leukemia designed to minimize long-term side effects. This program will include a major effort in leukemia immunology. More specifically, this will include the identification of subsets of leukemia through the use of leukemia specific antibodies and cell sorting: the use of similar techniques for the detection and quantification of minimal residual disease; and the use of leukemia specific antibodies and HLA matched lymphocytes programmed for cytotoxicity to leukemia cells in immunotherapy. In parallel with the above studies, supportive care techniques including granulocyte transfusions and prophylactic oral non-absorbable antibiotics in patients undergoing intensive treatment will be undertaken. In order to assess the cytokinetic status of the patients, particularly in complete remission, various colony forming unit and cytogenic techniques will be applied to determine whether remissions in AML represent true remissions in that the bone marrow is recolonized with normal hematopoietic tissue. Phase I and II studies of new agents for acute leukemia will be undertaken. Clinical pharmacologic studies of established agents as well as new agents will be conducted in parellel with this clinical therapeutic research.